Opposing effects of proteasomes and lysosomes on LIFR: Modulation by TNF
| Autor: | Weihong Pan, Chuanhui Yu, Abba J. Kastin, Hong Tu |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Lipopolysaccharides
STAT3 Transcription Factor Cytoplasm Proteasome Endopeptidase Complex Leukemia Inhibitory Factor Receptor alpha Subunit Transcription Genetic Receptor expression Down-Regulation Inflammation Leukemia inhibitory factor receptor Protein degradation Biology Cell Fractionation Cell Line Proinflammatory cytokine Cellular and Molecular Neuroscience Downregulation and upregulation medicine Animals Humans Extracellular Signal-Regulated MAP Kinases Tumor Necrosis Factor-alpha Ubiquitin Cell Membrane NF-kappa B Endothelial Cells General Medicine Rats Cell biology Proteasome Blood-Brain Barrier Tumor necrosis factor alpha medicine.symptom Lysosomes |
| Zdroj: | Journal of Molecular Neuroscience. 32:80-89 |
| ISSN: | 1559-1166 0895-8696 |
| Popis: | The blood-brain barrier (BBB), a communicating interface for inflammation, transports cytokines through its endothelial cells. This study shows how tumor necrosis factor alpha (TNF) regulates the expression of the leukemia inhibitor factor receptor (LIFR) gp190 in RBE4 cells. The high expression of LIFR was rapidly downregulated by the proinflammatory agents lipopolysaccharide, TNF, and LIF. Downregulation by TNF affected LIFR endocytosis and lysosomal degradation, preceding decreased LIFR mRNA. Lysosomal inhibitors reversed the rapid disappearance of LIFR, whereas inhibition of the ubiquitin-proteasome pathway did not. Rather, blockade of proteasome activity, as well as inhibition of NFkappaB activation, reduced the basal expression of LIFR. Thus, NFkappaB activity and proteasome degradation of IkappaB stabilized LIFR and prevented its rapid lysosomal degradation. By a non-NFkappaB-mediated mechanism, TNF facilitated LIFR degradation and reduced LIFR activation indicated by pStat3. The novel opposite effects of proteasomes and lysosomes in controlling receptor expression shows the functional implications and interactions of circulating inflammatory cytokines in acutely modulating BBB activity. |
| Databáze: | OpenAIRE |
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